DESCRIPTION: Gene targeting experiments have established unequivocally that the MyoD-family of transcription factors play key regulatory roles during embryonic skeletal-muscle development. By contrast, the role of the MyoD-family in adult skeletal muscle remains unclear. A role for MyoD in muscle regeneration is suggested by the observation that the MyoD is upregulated prior to satellite cell (the stem cell of adult muscle) proliferation and differentiation, and before expression of the remain factors. To test for a role for MyoD in muscle regulation,the investigator interbred MyoD mutant mice with the mdx mouse strain. The mdx mice are an animal model for Duchenne and Becker muscular dystrophies but unlike humans, skeletal muscle integrity is maintained by a high regenerative capacity. Their results indicate that mdx mice lacking MyoD display severe dystrophic changes in skeletal muscle leading to premature death around one year of age. They propose to further characterize by immunohistological and molecular analysis, the function of mutant, satellite cells in vivo and in vitro. To better understand the role played by MyoD, The investigator will examine skeletal muscle regeneration in mice overexpressing MyoD as a consequence of gene duplications generated by gene-targeting in embryonic stem cells. To investigate the mechanisms leading to satellite cell activation, they will examine expression of MyoD-LacZ transgenes to map the MyoD regulatory sequences required for this induction of MyoD transcription. This approach will also be used to determine the fate of satellite cells in mice lacking MyoD. Understanding how regulatory genes control the repair of skeletal muscle, in particular the formation, activation, proliferation, and terminal differentiation of satellite cells, is highly relevant to understanding the regenerative processes that occur in patients with different muscular dystrophies. Clearly, elucidating the function of MyoD in this regard should allow insights into the regeneration of skeletal muscle in health and disease, and potentially lead to novel therapies.